The administration of o-bromophenol (1.75 mmol/kg; i.p.) in male Sprague-Dawley rats, a metabolite of bromobenzene, caused a 50% decrease in renal glutathione levels within 90 min. In contrast hepatic glutathione levels decreased to only 80% of those in controls 5 hr after o-bromophenol administration. Doses of o-bromophenol required to deplete hepatic glutathione were greater than those required to deplete renal glutathione. Doses 1.28 mmol/kg were required decrease by 25% the glutathione level in kidney and liver respectively. o-Bromophenol at doses greater 1.6 mmol/kg caused severe renal necrosis in noninduced rats with consequent elevations in blood urea nitrogen (BUN) levels. To cause a similar toxicity a five fold larger dose of bromobenzene would have been required. Pretreatment of rats with either diethylmaleate or phenobarbital signficantly increased the BUN levels caused by o-bromophenol. In contrast, pretreatment of rats with piperonyl butoxide decreased BUN levels after o-bromophenol administration. Although 14C-o-bromophenol gave rise to covalently bound material in both liver and kidney in untreated rats, phenobarbital treatment increased the covalent binding to kidney but not to liver protein in vivo. Liver microsomes but not kidney microsomes converted o-bromophenol to 2-bromohydroquinone and covalently bound material. Doses greater than 0.53 mmol/kg of 2-bromohydroquinone to rats resulted in the elevation of BUN level and severe renal necrosis. Histopathological changes in kidney sections following 2-bromohydroquinone were indistinguishable from those observed following either bromobenzene or o-bromophenol administration.